1. Field
The present disclosure related to polypeptides inhibiting binding between a vascular endothelial growth factor and a vascular endothelial growth factor receptor, fusion proteins including the inhibiting polypeptides, and methods of preparing the fusion proteins.
2. Description of the Related Art
Angiogenesis is a process involving the growth of new blood vessels from existing vessels, which plays a vital role in formation of organs, normal biological growth, and wound healing. In addition, abnormal angiogenesis is known to be an important contributor to diseases such as development and metastasis of tumor cells, age-related macular degeneration, diabetic retinopathy, psoriasis, rheumatoid arthritis, and chronic inflammation.
The development and metastasis of tumor cells depend on angiogenesis. Thus, since it has been suggested that a hypothesis in which anti-angiogenesis therapeutic drugs would become novel anti-cancer therapeutic drugs, research into the mechanism of angiogenesis has been conducted to develop a new anti-cancer therapeutic drug. Among various angiogenesis factors, research into the function of vascular endothelial growth factor (VEGF) has been conducted most actively. When tumor tissues develop, the tumor tissues cause vessel regression and the tumor tissues are excessively grown to form a hypoxic environment therein. As a result, conditions where angiogenesis occurs are provided within the tumor tissue. Under the conditions, vascular endothelial cells increase expression of VEGF to form new vessels around tumor cells. Since the growth of the vascular endothelial cells and vascular formation are induced by expression of VEGF and reaction between VEGF and vascular endothelial growth factor receptor (VEGFR), the reactions described above are a vital process in angiogenesis. Thus, angiogenesis in tumor tissues is suppressed by inhibiting binding between VEGF and VEGFR, and a compound that inhibits binding between VEGF and VEGFR may become an anti-cancer drug candidate or provide a target for developing anti-cancer therapies. In addition, VEGF may emerge as effective target for anti-cancer therapy in that VEGF is a ligand initiating transduction by VEGFR of intracellular signals for vascular formation.
A humanized antibody binding to human VEGF is approved for treating colon cancer and rectal cancer. However, targeting VEGF using currently available therapies is not effective for all patients or other kinds of cancers.